Raman Spectroscopic Properties Of Anticancer Drug-metal Nanoparticles System

Cancer treatment has always been the direction of researchers.Traditional treatment options（radiotherapy,surgery,and chemotherapy）cannot cure cancer,and cannot solve the problems of easy recurrence and side effects.Therefore,a more effective treatment method is urgently needed.Metal nanoparticles are widely used in various fields due to their excellent properties.In recent years,due to the continuous efforts of scientific researchers,metal nanoparticles have shown great application potential in the medical field.For example,the surface of metal nanoparticles can be modified with anti-cancer active drugs,and the drugs can be used as drug carriers for delivery;metal nanoparticles with special properties can be targeted and stacked in cancer cells,and killed by the photothermal effect generated by near-infrared light at high temperature Cancer cells;some modified metal nanoparticles can kill cancer cells by generating reactive oxygen species in cancer cells through excitation light irradiation.The application of these metal nanoparticles in cancer therapy often requires surface modification with active anticancer drugs.The surface modification of metal nanoparticles is usually accomplished by the chemical adsorption of drug molecules on the surface of metal particles.Therefore,it has important research value to study the interaction between anticancer active drugs and metal surfaces.Surface-Enhanced Raman Spectroscopy（SERS）can provide information on the functional groups and electronic structure changes of molecules interacting with the surface,so it is widely used to confirm the adsorption state of molecules on the substrate surface.Density functional theory（DFT）is a quantum chemical calculation method that describes the properties of matter by solving the wave function,which can accurately describe the ground state properties,electronic properties,and reaction properties of molecules.SERS combined with density functional theory to jointly study the interaction and chemisorption effect between molecules and interfaces has been confirmed by many studies to be feasible.Therefore,this paper mainly uses SERS and density functional theory,supplemented by ultraviolet-visible spectroscopy,transmission electron microscopy characterization,combined with Raman spectroscopy,molecular frontier orbitals,molecular electrostatic potential and molecular binding energy to study:The chemisorption effect and Raman characteristics of anticancer active drug molecules and metal nanoparticles surface,and the adsorption conformation of molecules on the substrate;differences in molecular properties and Raman properties of anticancer active drug molecules with isomeric properties adsorbed on the substrate surface;differences in adsorption properties between different binding sites of anticancer active drug molecules and metal substrate docking;Molecular-metal charge transfer effect and the enhancement contribution provided by charge transfer effect in chemically enhanced and SERS;in the case of single metal and mixed metal substrates,the molecular and Raman properties of the interaction between molecules and substrates and other chemical parameters vary with the substrate.The main research contents and results of this paper are as follows:（1）The chemisorption effect between fenbendazole and gold nanoparticles was studied by UV-Vis spectrophotometry,density functional theory,Raman spectroscopy,and SERS.The results indicated that a chemisorption effect occurred between Fenbendazole and Au NPs.There are differences between theoretical and experimental spectra and the reasons for the difference between theoretical Raman spectra and experimental Raman spectra are explained.The chemical activity of Fenbendazole and Fenbendazole-Au₁/Au_3/Au₆ was studied by molecular frontier orbital theory,and it was found that the chemical activity was the strongest when Fenbendazole and Au₃ were chemisorbed.In addition,the spectral peaks at 851 cm^-1,1222 cm^-1,1425 cm^-1,and 1566 cm^-1 were selectively enhanced,which can be explained by selection rules and inferred that Fenbendazole is vertically adsorbed on the substrate surface by imidazole group.（2）The Raman activity spectra,frontier molecular orbitals,and molecular electrostatic potentials of the isomer molecules CBD（Cannabidiol）and THC（Tetrahydrocannabinol）and their respective gold complexes were studied using density functional methods.The phenomenon of"selective enhancement"of spectral peaks was observed in the Raman activity spectrum of the CBD-Au_n complex and the spectral Raman activity spectrum of the THC-Au_n complex.The molecular frontier orbital energy gap suggests that CBD is more chemically reactive than THC.CBD/THC has the strongest chemical activity and stronger charge transfer effect when it forms complexes with Au₃ atomic clusters.Molecular electrostatic potential（MEP）indicated that the electronegativity sites were adsorption sites for CBD/THC molecules and the gold surface.The MEP of CBD/THC complexes also demonstrated the existence of charge transfer effect between CBD/THC and Au.Both the phenomenon of"selectivity"in the Raman activity spectra of the complexes and the above assumptions can be explained by the surface selection rule.The adsorption conformation of CBD/THC molecules on gold surface was determined.The results showed that CBD was vertically adsorbed on the gold surface through the resorcinol structure,while THC was vertically adsorbed on the gold surface through the tetrahydropyran and benzene rings.（3）The chemisorption effect of Icotinib on the surface of Au NP was confirmed by UV-Vis spectroscopy and transmission electron microscopy（TEM）characterization.The molecular-related properties of Icotinib-Au₆ complexes were investigated using density functional theory methods.Four potential binding sites of the Icotinib molecule were predicted by the MEP of the Icotinib molecule.Binding energy calculations showed that Icotinib formed a stable complex by chemisorption of acetylene groups with Au₆ atomic clusters.The molecular frontier orbitals confirmed that the charge transfer effect occurred on the ethynyl,benzene,and quinazoline rings of the Icotinib molecule.The Herzberg-Teller surface selection rule is used to explain the selective enhancement phenomenon in theoretically calculated Raman spectroscopy.The Raman enhancement contribution brought by the charge transfer effect was evaluated.By comparing the theoretical spectrum and the experimental spectrum,it is found that the characteristic peaks have peak broadening and shifting,and the reasons for the peak broadening and shifting of the SERS compared with the normal Raman spectrum are explained.（4）Use the density functional method to carry out research from the theoretical level.Molnupiravir’s MEP has four highly electronegative chemisorption sites.The calculation results of binding energy prove that Molnupiravir undergoes stable chemisorption through these four adsorption sites and Au₆/Ag₆/Au₃Ag₃ atomic clusters.Among them,Molnupiravir is the most stable through chemisorption generated by O1 atoms and substrates.The molecular frontier orbitals of Molnupiravir and Molnupiravir complexes with Au₆/Ag₆/Au₃Ag₃ substrates were calculated.The molecular hardness,chemical potential,and other parameters of the complexes were evaluated,which proved that the Molnupiravir-Au₃Ag₃ composite nanomedicine system has good biological stability and safety.Finally,the Raman activity spectrum of the complexes formed by Molnupiravir and Au₆/Ag₆/Au₃Ag₃ was studied,and it was found that there was a phenomenon of spectral peak selectivity enhancement and the reason for this phenomenon was explained.The Raman enhancement of Molnupiravir and Au₃Ag₃ complex was found to be weaker than that of Molnupiravir and Au₃Ag₃ complex.The reason for this phenomenon was well explained by metal metallooptics.